When the Wake Forest (WF) Clinical and Translational Science Institute (CTSI) joined the CTSA consortium in August 2015, our goal was to use our resources to catalyze WF?s transformation into an exemplary Learning Health System in which ?science, informatics, incentives, and culture are aligned for continuous improvement and innovation, with best practices seamlessly embedded in the delivery process and new knowledge captured as an integral by-product of the delivery experience.? We seek to extend this framework by integrating traditional academic goals of T0 ? T4 discovery, translation, and scholarship to form a new vision?the Academic Learning Health System (aLHS). In our initial 3 years of funding, we have progressed towards our goal, establishing an integrated research governance model, with the CTSI at its core, to realize efficiencies and address roadblocks that hamper translational progress. We established Translational Catalysts to link the academic and clinical enterprises and designed training programs to develop the skills our workforce needs to make the aLHS a reality. We developed foundational informatics infrastructures essential to learning and growing, engaged communities and stakeholders to integrate diverse perspectives into the fabric of our aLHS, and created a milieu for nurturing innovative translational methods. We became a valued member of the CTSA national network, actively collaborating with 20 CTSA hubs, and shared our world-class nonhuman primate models with the consortium. With these successes, we turn to the next 5 years with strong assets in leadership, structure, scholarship, and culture that uniquely position us to realize the aLHS ideal. We will fully integrate our new Translational Catalysts ? biomedical informatics, implementation science, precision medicine, healthcare innovation, and clinical trials ? and use them, along with incentives for academic engagement, to mobilize our growing clinical network. We will develop, implement, and broadly disseminate improved methods and processes that will increase the efficiency, safety, and reproducibility of preclinical and clinical science. We will partner with our community to integrate special populations, and support health research across the lifespan. We will train our workforce for new roles, especially in team environments, with new training programs (e.g., TL1 aLHS Scholars Program, the Learning TREE online educational platform for individualized learning, Research-in-Action) and broaden our highly successful KL2 training for early-career faculty. We will serve as a hub for biomedical informatics, accelerating progress by enhancing existing resources, promoting collaboration and data sharing, and building new capacity. We will remain committed to inclusiveness, mutual respect, and multiple perspectives to act as a catalyst for change and healthy equity. We will further extend the reach of the aLHS into the communities served by our expanding health system and will broaden our collaborations with other CTSA hubs to share best practices and export the aLHS model ? all guided by our ultimate goal of improving the health of our region and nation.